stem cell homing and niche
StemCells干细胞具有疾病治疗的潜力
StemCells干细胞具有疾病治疗的潜力Stem Cells: Unlocking the Potential for Disease TreatmentIntroduction:The field of stem cell research has garnered tremendous attention in recent years due to its promise in revolutionizing disease treatment. Stem cells, with their unique ability to self-renew and differentiate into various specialized cell types, hold the potential to treat a wide range of diseases and injuries. This article explores the incredible therapeutic potential of stem cells, highlights their successful applications, and discusses the challenges associated with their use.Understanding Stem Cells:Stem cells are undifferentiated cells capable of developing into specialized cells and tissues in the body. They are classified into two main types: embryonic stem cells and adult stem cells. Embryonic stem cells are derived from early-stage embryos and possess the ability to differentiate into any cell type in the body. On the other hand, adult stem cells are found in various organs and tissues, capable of replenishing and repairing damaged cells within their respective locations.Therapeutic Potential of Stem Cells:1. Regenerative Medicine:Stem cells have the extraordinary potential to repair and regenerate damaged tissues and organs. This makes them a valuable tool in regenerative medicine, offering hope for patients suffering from debilitating diseases such as Parkinson's disease, Alzheimer's disease, and spinal cord injuries. By replacing or repairing damaged cells with healthy ones derived from stem cells, researchers believe they can restore lost functions and improve overall quality of life.2. Treatment of Blood Disorders:Stem cells are also utilized in the treatment of various blood disorders, including leukemia and lymphoma. Hematopoietic stem cell transplantation, also known as a bone marrow transplant, is a well-established procedure that involves replacing damaged or defective bone marrow with healthy stem cells. This therapy has saved countless lives and offers a potential cure for many patients with blood-related diseases.3. Cardiac Repair:Heart disease is a leading cause of death worldwide. Stem cells have shown significant potential in regenerating damaged heart tissues and improving heart function. Clinical trials have demonstrated promising results, with stem cell treatments leading to the formation of new blood vessels and the reduction of scar tissue caused by heartattacks. These advancements offer hope for individuals suffering from heart failure and other cardiac conditions.4. Treatment of Autoimmune Disorders:Autoimmune disorders occur when the immune system mistakenly attacks the body's own tissues. Stem cells can potentially modulate the immune response and suppress the abnormal immune reactions seen in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. This innovative therapy holds promise for managing and even reversing the progression of these chronic conditions.Challenges and Ethical Considerations:1. Ethical Concerns:Embryonic stem cells are extracted from human embryos, raising ethical concerns regarding the destruction of potential human life. These concerns have sparked debates and calls for strict regulations and guidelines in the field of stem cell research. However, alternative sources of stem cells, such as adult stem cells and induced pluripotent stem cells (iPSCs) derived from adult cells, offer promising alternatives that bypass these ethical dilemmas.2. Immune Rejection:One challenge in stem cell therapy is the risk of immune rejection. Stem cell-derived tissues and organs may be perceived as foreign by the recipient's immune system, leading to rejection and potential complications. Researchers are actively exploring ways to overcome this issue, such as using the patient's own cells or employing immunosuppressive drugs to prevent rejection.3. Tumor Formation:Stem cells have the potential to form tumors if they undergo uncontrolled growth and differentiation. This highlights the importance of rigorous testing and safety measures before any stem cell-based therapy is introduced into clinical practice. Researchers strive to ensure that the genetic stability and functionality of stem cells are carefully assessed to minimize the risk of tumor formation.Conclusion:Stem cells have ushered in a new era of medicine, offering immense potential for treating a wide range of diseases and conditions. The regenerative and therapeutic capabilities of stem cells are providing hope for patients with previously incurable disorders. However, further research, clinical trials, and ethical considerations are necessary to maximize the benefits and safety of stem cell-based therapies. With continued advancements, stem cell research is poised to change the landscape of medicine and greatly improve patient outcomes.。
干细胞-幻灯
1999年12月 1999年12月，美国 科学》 《科学》杂志公布了 当年世界科学进展的 评定结果， 评定结果，干细胞的 研究成果列在举世瞩 目耗资巨大的人类基 因组工程之前， 因组工程之前，名列 十大科学进展首位。 十大科学进展首位。
六、ES细胞研究面临的问题 ES细胞研究面临的问题
1. 用于干细胞研究的胚胎来源困难 2. 如何保持胚胎干细胞的全能性 3. 干细胞在体外发育成完整的器官尚难以做到 4. 分化细胞移植仍有可能发生免疫排斥 5. 安全性问题 分化后的细胞是否有致瘤性？ (1) 分化后的细胞是否有致瘤性？ (2) 动物细胞携带的病毒感染人类 6. 法律和伦理问题
人体早期发生过程： 人体早期胎干细胞的定义: 人胚胎干细胞的定义:
受精后72 72h 受精后5 卵裂 受精后72h 受精后5-7天 胚泡（囊胚） 合子 卵裂球 桑椹胚 胚泡（囊胚）
胚泡
滋养层— 滋养层—>胎儿附属结构 囊胚腔 内细胞群— 胚盘— 内细胞群—>胚盘—>胚体
红色细胞：神经元 红色细胞： 绿色细胞： 绿色细胞：胶质细胞
胚胎干细胞脑内移植后分化为神经前体 细胞（ 图中红色细胞） 细胞（A图中红色细胞）和卫星细胞 图中红色细胞） （B图中红色细胞）
诱导成胰岛素分泌细胞
（1）5阶段诱导法： 阶段诱导法： 巢蛋白（nestin)分泌细胞 ES 类胚体 巢蛋白（nestin)分泌细胞 胰岛素 分泌细胞 3-磷酸肌醇-激酶抑制剂为重要的诱导剂 磷酸肌醇（2）基因转染：胰岛β细胞分化相关基因Pax 1和 基因转染：胰岛β细胞分化相关基因Pax 1和 Pax 4
治疗性克隆（ 治疗性克隆（therapeutic cloning ）：
去核卵细胞 + 受者体细胞核 分离内细胞群 分化 移植治疗 克隆 囊胚 ES细胞建系 ES细胞的诱导 ES细胞建系 ES细胞的诱导
皮肤干细胞
Chemical compound screen
Translational research
3. Hair regeneration
- Stress hormone - Fat - Pregnancy change - Aging
Preview
1. Introduction of skin as a model system 2. Skin stem cell identification 3. Skin stem cell niche 4. Hair follicle stem cell self-renewal 5. Hair follicle stem cell specification
Designated SC vs. Population neutral competition
Benjamin D. Simons, et al., 2012
Melanocyte stem cell and dominant niche
Nishimura EK, et al., 2002
Melanocyte stem cell and dominant niche
Ting Chen, et al., 2012
In vitro RNAi screen for HFSCs self-renewal regulators
Ting Chen, et al., 2012
In vitro RNAi screen for HFSCs self-renewal regulators
1. Slow cycling 2. In vitro long-term self-renew 3. Multipotency in graft assay
干细胞niche与心肌细胞分化的调控机制研究
干细胞niche与心肌细胞分化的调控机制研究余细勇【期刊名称】《中山大学学报（医学科学版）》【年(卷),期】2011(032)002【摘要】Stem cells are the special cells of self-renewal and differentiation potential. Recent studies found that the biological behaviors of stem cells are highly dependent on their microenvironment (niche). There are two roles of niche on stem cells: the direct effects between cell contacts, and the indirect effects such as matrix and cytokines which involve in several signal transduction pathways and their cross-talks. Here, we mainly describe the effects of bone marrow niche on mesenchymal stem cells (SMC), and the regulatory mechanisms of MSC differentiation into myocardial cells.%干细胞是一类具有自我更新和多向分化潜能的特殊细胞.研究发现,干细胞的生物学行为高度依赖于其所处的微环境(niche).Niche对干细胞的作用分为细胞与细胞之间的直接作用和基质及众多细胞因子对干细胞的间接作用,涉及多条信号转导通路及其相互作用.本文主要介绍骨髓干细胞的niche对间充质干细胞(MSC)的调控,并探讨MSC向心肌细胞分化的调控机制.【总页数】6页(P141-145,154)【作者】余细勇【作者单位】广东省医学科学院//广东省人民医院,医学研究中心,广东,广州,510080【正文语种】中文【中图分类】R54【相关文献】1.鹿茸多肽诱导心肌干细胞向心肌细胞分化的机制研究 [J], 王艳玲;黄晓巍;李哲;何璐;徐岩;曲晓波2.益气补肾方调控胃癌干细胞 niche 及Notch 信号通路抗转移分子机制研究 [J], 刘云霞;徐叶峰;蒋沈君;姚勇伟;王娜3.精原干细胞分化及自我更新调控机制研究进展 [J], 韩济南;候艳秋;吴绍华4.RNA联合信号通路调控脂肪干细胞分化的机制研究分析 [J], 李军最;马鸳霞;黄克;李林;李兴艳;张波;胡敏;梁红锁;蔡敏;杜勇军5.Wnt/β-catenin信号通路在体外调控诱导性多能干细胞向神经干细胞分化中的作用及机制研究 [J], 周丽萍;林德菊;周斌杰;姚盼盼;余勤因版权原因，仅展示原文概要，查看原文内容请购买。
肾脏的再生机制
万方数据暨照遗董适堑竖整煎苤姜筮１２踅笙！翅婴！！生堕旦１４周时ＣＤ２４＋ＣＤｌ３３＋前体细胞明显减少，此时终末分化的肾单位已经出现，在发育成熟的肾脏中，此类细胞占的比例不足２％¨引。
最近，有研究在成年小鼠模型中进一步证实了肾小球壁层上皮细胞代表了一群具有再生能力的肾脏固有前体细胞。
而且，体外诱导壁层上皮细胞上皮一问充质细胞转分化可使其表达胚肾前体细胞的表型，再将其注射至单侧肾切除小鼠模型后，在植入３周后可以再生新的肾脏组织，包括小球和小管结构０１肾小管的再生机制急性肾小管损伤后，肾脏可启动再生机制，从而使大部分患者的肾功能得以恢复，但是对再生细胞的来源却知之甚少…。
目前研究认为急性肾小管损伤的修复主要是由邻近未受损小管上皮细胞增殖完成，增殖细胞霞新衬附在裸露的小管基膜上，最终修复肾小管的结构和功能１９Ｊ。
而且，目前也有一些研究表明小管上皮细胞可以在急性肾损伤时自我更新，分化的小管细胞迁移至邻近部位替代死亡细胞¨５Ｊ。
因为小管上皮细胞停留在Ｇ１期而不是Ｇ０期，所以在损伤后可以迅速启动增殖反应，修复肾小管。
然而，在慢性或广泛性的肾小管损伤时，上述机制则难以奏效，此时肾脏固有干细胞被活化并在小管再生中起关键作用¨引。
近来发现的定位于鲍曼囊尿极的ＣＤ２４＋ＣＤｌ３３＋前体细胞可能正是参与小管再生的固有细胞。
从结构特点来看，虽然近曲小管从鲍曼囊发出的角度不一，但是在管球连接部至少有部分细胞是中间类型，在壁层上皮细胞上有典型的小管微绒毛结构¨川，这些发现说明壁层上皮细胞可能转化为小管上皮。
相应地，离体的成人肾脏ＣＤ２４＋ＣＤｌ３３＋前体细胞在急性肾损伤的小鼠模型中可以再生新的小管结构，在结构和功能上减轻肾脏损伤¨ｋ１２１。
在梗阻性肾病、中毒性。
肾病、慢性移植肾肾病等慢性小管间质性疾病中，管球连接部损伤是临床上的一个普遍特征¨８｜。
综合上述研究结果可以看出，小管再生在大多数情况下由邻近小管细胞增殖所完成，但在重度或慢性损伤时，位于鲍曼囊尿极的壁层上皮细胞可能参与小管再生过程（图１），其具体机制仍需进～步研究阐明。
Stem Cell Biology and Regenerative Medicine
Stem Cell Biology and Regenerative Medicine Stem cell biology and regenerative medicine are fields that have gained significant attention in recent years. Stem cells are unique cells that have the ability to differentiate into various cell types and have the potential to regenerate damaged tissues. The field of regenerative medicine aims to use stem cells to replace or repair damaged tissues and organs in the body. While the potential benefits of stem cell research and regenerative medicine are vast, there are also ethical concerns and challenges that need to be addressed.One of the main ethical concerns surrounding stem cell research is the use of embryonic stem cells. Embryonic stem cells are derived from embryos that are typically discarded after in vitro fertilization. Some individuals argue that using these embryos for research purposes is unethical and violates the sanctity of human life. Others argue that the potential benefits of stem cell research outweigh these concerns and that the embryos used for research would have been discarded anyway.Another ethical concern is the potential for the commercialization of stem cells. As stem cell research continues to advance, there is a growing market for stem cell therapies. Some companies are already offering stem cell treatments for various conditions, despite the lack of sufficient clinical trials and regulatory oversight. This raises concerns about the safety and efficacy of these treatments, as well as the potential for exploitation of vulnerable patients.In addition to ethical concerns, there are also scientific and technical challenges that need to be addressed in the field of regenerative medicine. One major challenge is the ability to control the differentiation of stem cells into specific cell types. While stem cells have the potential to differentiate into any cell type, directing them to differentiate into a specific cell type can be difficult. This can limit the effectiveness of stem cell therapies and increase the risk of complications.Another challenge is the potential for immune rejection of transplanted stem cells. Since stem cells can differentiate into any cell type, they can potentially be used to replace damaged tissues and organs. However, the immune system may recognize thesetransplanted cells as foreign and mount an immune response, leading to rejection of the transplanted cells. This can limit the effectiveness of stem cell therapies and increase the risk of complications.Despite these challenges, the potential benefits of stem cell research and regenerative medicine are vast. Stem cells have the potential to revolutionize the treatment of a wide range of conditions, including cancer, heart disease, and neurological disorders. Stem cell therapies could also reduce the need for organ transplants and improve the quality of life for millions of people around the world.In conclusion, stem cell biology and regenerative medicine are fields that hold great promise for the future of medicine. While there are ethical concerns and scientific challenges that need to be addressed, the potential benefits of these fields are vast. As research in these areas continues to advance, it is important to ensure that ethical considerations are taken into account and that the safety and efficacy of stem cell therapies are rigorously tested. With careful consideration and continued research, stem cell biology and regenerative medicine could transform the way we treat a wide range of conditions and improve the lives of millions of people around the world.。
武汉干细胞原理
武汉干细胞原理解析1. 什么是干细胞？干细胞是一类具有自我更新和多向分化潜能的特殊细胞。
它们可以不断地自我复制，产生相同类型的干细胞，同时还可以分化成各种不同类型的细胞，如神经细胞、心肌细胞、肝脏细胞等。
这种特殊能力使得干细胞在医学研究和治疗上具有巨大的潜力。
2. 干细胞分类根据来源和发育阶段的不同，干细胞可以分为两大类：胚胎干细胞和成体干细胞。
2.1 胚胎干细胞（Embryonic Stem Cells）胚胎干细胞是从早期发育阶段的受精卵中获得的。
这些受精卵通常来自于试管婴儿或不孕治疗过程中被捐赠或丢弃的受精卵。
由于这些受精卵尚未发育为一个完整的个体，因此提取其中的内部组织群块（内细胞团）时，不会对个体造成任何伤害。
胚胎干细胞具有极高的多向分化潜能，可以分化成人体内的任何一种细胞类型。
这使得它们在研究和治疗上具有广泛的应用前景。
2.2 成体干细胞（Adult Stem Cells）成体干细胞存在于已经发育完全的个体中，分布在各个组织和器官中。
这些干细胞主要负责组织修复和再生。
相比于胚胎干细胞，成体干细胞的多向分化潜能较低，通常只能分化成与其来源组织相关的细胞类型。
3. 干细胞在医学上的应用由于其独特的特性，干细胞在医学领域有着广泛的应用前景。
3.1 组织修复和再生干细胞可以分化成各种类型的功能性细胞，并替代受损或死亡的组织。
例如，在心脏病患者中使用心肌干细胞可以修复受损的心肌组织，恢复心脏功能。
同样地，使用神经干细胞可以帮助治疗神经退行性疾病，如帕金森病和脊髓损伤。
3.2 药物筛选干细胞可以用于药物的筛选和评估。
通过将药物作用于干细胞，可以模拟人体内药物对不同类型细胞的影响，从而评估其毒性和效果。
这种方法可以减少动物实验的需求，并提高药物研发的效率。
3.3 疾病机制研究利用干细胞可以模拟人体内的各种细胞类型，从而深入研究各种疾病的发生机制。
例如，通过将患者特定类型的干细胞分化成神经细胞，可以观察和分析与神经退行性疾病相关的异常变化，为新药开发和治疗方法提供依据。
干细胞
Stem cells within their niche in the bone marrow. (A) Schematic diagram of hematopoietic and niche cellular components in the bone marrow. The exact spatial relationships are not well defined. (B) Candidate extrinsic signaling pathways that regulate proliferation and differentiation of HSCs. The colors represent the potential cellular elements that send and receive signals as in (A).
a,C. elegans germline divisions during development are symmetric with respect to size and morphology of daughter cells, cleavage plane and position. Continued mitotic divisions rely on signalling from the stem-cell niche. Stem cells are orange; differentiated cells are green; the stem-cell niche is red. b, Elimination of one or more germ cells by laser ablation (marked with a cross) during early (shown) or later larval development does not affect the ability to generate pools of stem cells and differentiated cells. Mitotic germ cells are therefore developmentally equivalent. c, Repositioning the niche induces germline stem cells at the new position. d, Niche duplication results in duplication of the germline stem-cell pool. Niche duplication has been accomplished by alterations in either the cell-cycle machinery or regulators of niche specification.
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• niche 的概念最早是在1978 年由Schofield 针 对造血干细胞的特殊微环境而提出的, 随后在 消化道、神经系统和性腺等组织也发现类似的 niche 结构。 • 干细胞通过与niche 内其它细胞和细胞因子等 的相互作用, 进行自我更新和定向分化, 从而 保护干细胞不受各种信号的干扰, 同时又防止 干细胞的过度增殖导致恶癌变。
羊膜与干细胞龛
• 夏照帆：An epidermal stem cells niche microenvironment created by engineered human amniotic membrane • Proteomic analysis of epithelium-denuded human amniotic membrane as a limbal stem cell niche. • Ex vivo expansion of limbal epithelial stem cells: amniotic membrane serving as a stem cell niche.
干细胞Homing及干细胞Niche
——关于干细胞归巢综述
干细胞Homing
归 巢
• 干细胞植入“微环境”并进一步自我更新和增生 分化的过程称为干细胞的“归巢”。 • “归巢” 用于形容细胞(特别是白细胞)趋向性迁 移并定植到特定靶向组织的过程。
定植/居
干细胞归巢机制
两种推测
• 其一：组织损伤后→信号释放→干细胞龛动员干 细胞→迁移至外周血→在损伤组织表达特异性受 体或配体引导下→干细胞移动并黏附于损伤处。 • 其二：干细胞动态循环于各组织间，仅在损伤发 生时才离开血循环渗入损伤处。 • 上述两种观点都认为循环的干细胞来源于干细胞 龛。
Niche与干细胞的关系
• 当Niche中的干细胞不存在时，Niche的结 构仍然可以保持，并为补充进来的细胞提 供维持干细胞能力方面的支持。
• 在一定的条件下，外来细胞可以通过占据 空的或功能异常的niche，移走内源干细胞 等方式直接进入组织，行使干细胞功能。
龛对干细胞的调控
• • • • Wnt信号途径 Shh信号途径 Notch信号途径 BMP信号途径
外源性干细胞归巢
两种假说
• 其一，给药后外源性干细胞直接进入损伤组织及 其他健康组织。 • 其二，给药后外源性干细胞干细胞需跨越血管内 皮细胞和细胞外基质进入干细胞龛，而后再游出。
• 目前外（异）源性干细胞移植治疗疾病还 处于基础研究阶段。 • 临床较成熟的两种干细胞移植为造血干细 胞和骨髓干细胞。 • 羊膜干细胞移植也仍处于基础研究阶段， 对于其homing机制、疗效的研究有待进一 步追踪。
Stem cell Niche
• 池→龛→微环境→小生境
• 干细胞在体内的自我复制以及产生起始分化 的子细胞的能力在维持组织平衡状态和持续 提供新细胞以替代生存时间短但高度分化的 细胞类型（如血液、皮肤和精子）等方面非 常关键。
• 干细胞的数量、分裂、自我复制和分化可能 受到细胞内在因素和周围微环境的外在信号 的共同调节。这些周围微环境被称为干细胞 特殊小生态环境，即干细胞的niche。源自• 主要参考书籍（文献略）
归巢过程
• 动员 • • • • •
粘附 趋化迁移
跨内皮游出
入侵
繁殖
外源性干细胞归巢
两种假说
• 其一，给药后外源性干细胞直接进入损伤组织及 其他健康组织。 • 其二，给药后外源性干细胞干细胞需跨越血管内 皮细胞和细胞外基质进入干细胞龛，而后再游出。
外源性干细胞归巢
两种假说
• 其一，给药后外源性干细胞直接进入损伤组织及 其他健康组织。 • 其二，给药后外源性干细胞干细胞需跨越血管内 皮细胞和细胞外基质进入干细胞龛，而后再游出。
Stem Cell Niche
具有支持细胞(support cell)，基膜(basement membrane).，联接分子等基本要素
Niche的特点
• 具有精确的空间结构，并提供足够的增殖和 抗凋亡信号，帮助排除促分化因子，以维持 干细胞全能性和自我复制的能力。 • 与干细胞密切接触的其他细胞或基膜是 Niche中控制干细胞行为信号的重要来源。 • Niche在维持组织功能方法具有很重要的作 用，破坏Niche可能会导致组织退化、衰老 以及形成肿瘤。